The ultimate goal of this project is the development of a liver cell culture system most suitable for studies of in vitro chemical carcinogenesis. Such a system should retain (1) in vivo levels of the different types of cytochrome P450, which activate carcinogens, and (2) inducibility by chemicals of cytochrome P450 to levels equivalent to those in the liver embryonic as well as adult chickens. Cultures of embryonic chick liver cells in a totally defined medium have been found, in the initial period of the research (1977-80), to retain these properties and to also retain inducibility of some of the Phase II reactions of activated carcinogens such as glucuronidation. We aim to characterize these properties more extensively and to apply the methods developed for the chick system to rat liver cultures in attempts to induce and maintain cytochrome P450 in the rat cells. We intend to determine whether the chick liver system activates carcinogens to forms which initiate DNA repair synthesis. The effects of bezo(a)pyrene and chromium on DNA of the chick cells will be assessed as well as the mechanism whereby cobalt decreases cytochrome P450.